Little is known about the nature of circulating parathyroid hormone in clinical disease. It is the purpose of this project to isolate parathyroid hormone, determine the structure of the polypeptide, elucidate the mechanism of action of the hormone, and to develop a clinically useful test for circulating parathyroid hormone. From these studies it is expected that one can understand the pathophysiology of certain metabolic diseases of bone and endocrine disturbances. The entire structures of bovine, porcine and human parathyroid hormone have been determined. Synthetic polypeptides representing the first 34 residues of bovine and human parathyroid hormone have been prepared. These molecules show all the biological properties of the native hormonal polypeptide. A highly sensitive radioimmunoassay for the hormone has been developed and is being modified further for potential use as a specific clinical tool. Studies show that the mechanism of action of the hormone is mediated through direct hormonal activation of adenylate cyclase in bone and kidney. An isolated parathyroid cell system has been developed that allows studies of secretagogues for parathyroid hormone.